Biophysical characterization of the insertion of two potent antimicrobial peptides-Pin2 and its variant Pin2[GVG] in biological model membranes

Bertrand, Brandt; Munusamy, Sathishkumar; Espinosa-Romero, José-Francisco; Corzo, Gerardo; Sosa, Iván Arenas; Galván‐Hernández, Arturo; Ortega‐Blake, Iván; Hernández-Adame, Pablo Luis; Ruíz-García, Jaime; Velasco-Bolom, José-Luis; Garduño‐Juárez, Ramón; Muñóz-Garay, Carlos

doi:10.1016/j.bbamem.2019.183105

Cited by 17 publications

(5 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the behavior of membranes within the pore formation process was studied in the CG simulations. Many MD simulations, either AA or CG, have shown that AMPs cause local perturbation in the target lipid bilayers. ,,, The CG simulation results align with the AA simulation results and show that the lipid acyl chains were disordered in the peptide location (Figure A–C). The peptides have a more disordering effect on the anionic membrane.…”

Section: Results and Discussionsupporting

confidence: 63%

Molecular Insights into Pore Formation Mechanism, Membrane Perturbation, and Water Permeation by the Antimicrobial Peptide Pleurocidin: A Combined All-Atom and Coarse-Grained Molecular Dynamics Simulation Study

et al. 2021

View full text Add to dashboard Cite

The antimicrobial peptide (AMP) pleurocidin has a broad antimicrobial activity against Gram-negative and Gram-positive bacteria by perturbation and permeabilizing their membranes; however, understanding the mechanism of action of pleurocidin, a promising AMP for replacing current antibiotic agents, has tremendous importance for future applications. Hence, we applied all-atom (AA) and coarse-grained (CG) molecular dynamics (MD) simulations to provide molecular-level insights into the pore-forming process. The early stages of pore formation were examined by 500 ns AA simulations. The results demonstrated that pleurocidin has the ability to create a pore with two peptides through which water molecules can flow. However, the results of the 25 μs CG simulations indicate that the final pore will be created by accumulation of more than two peptides. The results show that after 2.5 μs of simulations, peptides will aggregate and create a channel-like pore across the membrane. Pleurocidin can construct a more efficient and stable pore in the anionic membranes than in the zwitterionic membranes. Moreover, the structure amphipathicity, polarity, and basic residues play crucial roles in the pore formation and flow of water molecules across the lipid bilayers. In general, the findings revealed that based on the lipid compositions of the membranes, pleurocidin could act by forming either toroidal or disordered toroidal pores with different peptide arrangements.

show abstract

Section: Results and Discussionsupporting

confidence: 63%

Molecular Insights into Pore Formation Mechanism, Membrane Perturbation, and Water Permeation by the Antimicrobial Peptide Pleurocidin: A Combined All-Atom and Coarse-Grained Molecular Dynamics Simulation Study

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Molecular Dynamics (MD) simulations are a useful tool to investigate peptide-lipid bilayer interaction at atomic resolution. The interactions of different peptides with membrane, such as BMAP-28 and its analog [ 27 ], cathelicidins [ 28 ], magainin [ 29 ], Pin2 and its variant Pin2[GVG] [ 30 ], maculatin 1.1 [ 31 ], and megin peptide (M1) [ 32 ] revealed important molecular details and biomolecular processes. The conventional MD method modeled the system using residues with constant charges, not sampling the protonation states of titrable residues.…”

Section: Introductionmentioning

confidence: 99%

Modulatory Effects of Acidic pH and Membrane Potential on the Adsorption of pH-Sensitive Peptides to Anionic Lipid Membrane

et al. 2021

View full text Add to dashboard Cite

Anionic lipid membrane electrostatic potential and solution pH can influence cationic peptide adsorption to these bilayers, especially those containing simultaneously acid and basic residues. Here, we investigate the effects of the pH solution on MP1 (IDWKKLLDAAKQIL-NH2) adsorption to anionic (7POPC:3POPG) lipid vesicles in comparison to its analog H-MP1, with histidines substituting lysines. We used the association of adsorption isotherms and constant pH molecular dynamic simulations (CpHMD) to explore the effects of membrane potential and pH on peptides’ adsorption on this lipid membrane. We analyzed the fluorescence and zeta potential adsorption isotherms using the Gouy–Chapman theory. In CpHMD simulations for the peptides in solution and adsorbed on the lipid bilayer, we used the conformations obtained by conventional MD simulations at a μs timescale. Non-equilibrium Monte Carlo simulations provided the protonation states of acidic and basic residues. CpHMD showed average pKa shifts of two to three units, resulting in a higher net charge for the analog than for MP1, strongly modulating the peptide adsorption. The fractions of the protonation of acidic and basic residues and the peptides’ net charges obtained from the analysis of the adsorption isotherms were in reasonable agreement with those from CpHMD. MP1 adsorption was almost insensitive to solution pH. H-MP1 was much more sensitive to partitioning, at acidic pH, with an affinity ten times higher than in neutral ones.

show abstract

“…Most of recent experimental studies on AMP aim to investigate the effect of synthetic variants, suitably engineered, able to mimic and/or improve antimicrobial properties of natural ones while reducing the hemolytic activity. This is the case of Bertrand and co-workers [90] that evaluated the effects of a derivative of Pandinin 2, Pandinin 2 [GVG], on SLBs mimicking both prokaryotic and eukaryotic cells. The [GVG] residue was firstly engineered into Pandinin 2 by Rodriguez et al based on the evidence that peptides presenting this motif show high antimicrobial activity, but low or no hemolytic activity [25].…”

Section: Interaction Of Amps and Derivatives With Planar Model Lipid-...mentioning

confidence: 99%

The potential of AFM in studying the role of the nanoscale amphipathic nature of (lipo)-peptides interacting with lipid bilayers

et al. 2022

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) and lipopeptides (LPs) represent very promising molecules to fight resistant bacterial infections due to their broad-spectrum of activity, their first target, i.e. the bacterial membrane, and the rapid bactericidal action. For both types of molecules, the action mechanism starts from the membrane of the pathogen agents, producing a disorganization of their phase structure or the formation of pores of different size altering their permeability. This mechanism of action is based on physical interactions more than on a lock-and-key recognition event and it is difficult for the pathogens to rapidly develop an effective resistance. Very small differences in the sequence of both AMPs and LPs might lead to very different effects on the target membrane. Therefore, a correct understanding of their mechanism of action is required with the aim of developing new synthetic peptides, analogues of the natural ones, with specific and more powerful bactericidal activity. Atomic force microscopy (AFM), with its high resolution and the associated force spectroscopy resource, provides a valuable technique to investigate the reorganization of lipid bilayers exposed to antimicrobial or lipopeptides Here, we present AFM results obtained by ours and other groups on the action of AMPs and LPs on supported lipid bilayers (SLBs) of different composition. We also consider data obtained by fluorescence microscopy to compare the AFM data with another technique which can be used on different lipid bilayer model systems such as SLBs and Giant Unilamellar Vesicles (GUVs). The outcomes here presented highlight the powerful of AFM-based techniques in detecting nanoscale peptide-membrane interactions and strengthen their use as an exceptional complementary tool to in vivo investigations. Indeed, the combination of these approaches can help decipher the mechanisms of action of different antimicrobials and lipopeptides at both the micro and nanoscale levels, and to design new and more efficient antimicrobial compounds.

show abstract

Biophysical characterization of the insertion of two potent antimicrobial peptides-Pin2 and its variant Pin2[GVG] in biological model membranes

Cited by 17 publications

References 69 publications

Molecular Insights into Pore Formation Mechanism, Membrane Perturbation, and Water Permeation by the Antimicrobial Peptide Pleurocidin: A Combined All-Atom and Coarse-Grained Molecular Dynamics Simulation Study

Molecular Insights into Pore Formation Mechanism, Membrane Perturbation, and Water Permeation by the Antimicrobial Peptide Pleurocidin: A Combined All-Atom and Coarse-Grained Molecular Dynamics Simulation Study

Modulatory Effects of Acidic pH and Membrane Potential on the Adsorption of pH-Sensitive Peptides to Anionic Lipid Membrane

The potential of AFM in studying the role of the nanoscale amphipathic nature of (lipo)-peptides interacting with lipid bilayers

Contact Info

Product

Resources

About